CN101711710B - Medicament eluting stent and preparation method thereof - Google Patents
Medicament eluting stent and preparation method thereof Download PDFInfo
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- CN101711710B CN101711710B CN 200910246768 CN200910246768A CN101711710B CN 101711710 B CN101711710 B CN 101711710B CN 200910246768 CN200910246768 CN 200910246768 CN 200910246768 A CN200910246768 A CN 200910246768A CN 101711710 B CN101711710 B CN 101711710B
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- Materials For Medical Uses (AREA)
Abstract
The invention relates to a medicament eluting stent, which consists of a bare stent and a coating coated on the bare stent. The medicament eluting stent is characterized in that the coating at least comprises a polymer layer and a resin layer, wherein the polymer layer comprises polylactic-co-glycolic acid (PLGA) and medicaments; and the resin layer is coated on the surface of the polymer layer. A resin of the invention is coated on the surface of the medicament-loaded polymer coating. Due to the sustained release effect of the resin, on the premise of guaranteeing medicament dosage, the dosage of the polymer is reduced so as to obvious reduce an inflammatory reaction, reduce the generation of adverse reactions such as late intravascular restenosis and the like, and avoid forming late thrombosis.
Description
Technical field
The present invention relates to a kind of support, particularly a kind of bracket for eluting medicament of surface-coated resin.
Background technology
Extensive use along with Percutaneous Intracoronary Arterial Stenting, the development of the increase of clinical disease number of cases, the prolongation of following up a case by regular visits to the time and intravascular ultrasound technology, in-stent restenosis (ISR) problem just exposes gradually and more and more comes into one's own, and has become the research emphasis that gets involved the cardiology field.The recurrence of many patients with coronary heart disease ischemic event after accepting stent in the treatment is how relevant to ISR, in bare metal stent (BMS) epoch, the sickness rate of ISR can reach Stent patient's 15～30%, the ISR patient that only in global range in 1997, hospital gathers just reaches more than 100,000 examples, U.S.'s incomplete statistics in 1999 just has 150,000 examples, and real whole ISR patient may also run far deeper than so.The appearance of coating stent of medicine (DES) and development have represented an innovative technology of coronary heart disease treatment, it is the important breakthrough of coronary heart disease treatment, DES suppresses the formation of local new intima by the sustained release anti-proliferative drugs, effectively solved the restenosis problem that neointimal hyperplasia causes, made the incidence rate of ISR be reduced to 5～10%.Just because of its effectiveness, use the ratio of DES more and more higher in arteria coronaria is got involved, but new problem also occurs thereupon---be the advanced thrombus incidence rate of DES higher than BMS, incidence of thrombus increases to some extent, the DES that has gone on the market does not at present solve ISR, and has just postponed restenosis.Compare with BMS, although restenosis rate obviously reduces, absolute quantity is still very important.
Bracket for eluting medicament is with medicine directly or be applied to metal support surface by suitable carrier, becomes the local delivery system of medicine, and carrier has two kinds of degradable and non-degradable materials.In bracket for eluting medicament, suppress in-stent restenosis by sustained release.
Two kinds of bracket for eluting medicament that authenticated by U.S. FDA at present
Stent and
Stent is obtaining significant curative effect aspect reduction in-stent restenosis incidence rate.The medicine that they adopt respectively is rapamycin and paclitaxel.For prolong drug release time,
Stent uses polyvinyl vinyl acetate/polybutyl methacrylate (PEVA/PBMA) polymer coating as pharmaceutical carrier,
Stent uses copolymer (SIBS) polymer coating of styrene and polyisobutylene as pharmaceutical carrier.These two kinds of polymer are the non-degradable polymer.The non-degradable material retains in blood vessel wall, and the untoward reaction such as material aging, cracking and chronic inflammatory disease are arranged, and has increased the incidence rate of later stage thrombus in stents and in-stent restenosis.Due to the permanent residual problem that causes of using polymer in non-degradable polymer DES, people place hope on and use biodegradable polymers DES instead and make up these defectives.
Degraded in the degradation material certain hour, during also produce inflammatory reaction, increased the generation of the untoward reaction such as Restenosis in late period and the formation of advanced thrombus.The possible cause of generally acknowledging at present has that polymer or drug allergy, drug release are inhomogeneous, polymer degradation speed, coating cracking or come off, support is adherent bad etc.
On the other hand, in order to reach desirable therapeutic effect, must keep sufficient medication amount on support.On bracket for eluting medicament, the effect of pharmaceutical carrier is divided into and the adhesive effect of rack surface and the reservoir effect of control drug release substantially.Generally speaking, if improve medicine for the not only adhesive effect reduction of ratio of carrier, and also mostly reduce as the effect of reservoir.Being medicine increases for the ratio of carrier, not only is accompanied by the support expansion, and the danger of coating stripping or cracking increases, and the probability that medicine discharges end at short notice increases.
Extend its release time in order to improve drug level, must increase medicine and polymer use amount, and because increasing of polymer increased the probability of inflammatory reaction generation and may cause a series of untoward reaction.Therefore, in order to reduce the generation of the untoward reaction such as Restenosis in late period, reduce the risk that advanced thrombus forms, not only will select suitable pharmaceutical carrier to reduce inflammatory reaction, also will improve to the release behavior of medicine being only the necessary ways of optimizing DES.
Summary of the invention
The object of the present invention is to provide a kind of bracket for eluting medicament of coated with resins, this support has thinner polymer coating, also optimized the drug release behavior when reducing polymer volume, thereby limited inflammatory reaction, reduce the generation of the untoward reaction such as Restenosis in late period, reduced the risk that advanced thrombus forms.
Purpose of the present invention is achieved through the following technical solutions: a kind of bracket for eluting medicament, consisted of by bare bracket, the coating that is coated on support, it is characterized in that: described coating contains polymeric layer and resin bed at least, wherein, described polymeric layer comprises polylactic-co-glycolic acid (PLGA) and medicine; Described resin bed is coated on the polymeric layer surface.
Biodegradable material polylactic acid-glycollic acid (PLGA) is synthesized by ring opening copolymer by PGA (PGA) and polylactide (PLA).PGA (PGA) and polylactide (PLA) belong to polylactone family macromolecule material together, because they are all nontoxic, good biocompatibility, and hydrolysis can occur after meeting water in the ester bond that exists in their molecular backbones, cause the molecular backbone fracture, molecular weight reduces, and can being become carbon dioxide and water in vivo by tricarboxylic acid cycle, the final degradation product, glycolic acid of PGA and polylactide and lactic acid excretes, therefore these two kinds of polylactone family macromolecule materials all can finally disappear in body due to the biodegradation of material after implanting fully.By the adjusting to PLGA ratio of components and molecular weight, the biodegradation rate of PLGA (degradation half life) can be regulated more than some months to a year, and the composition that the drug release behavior also can be by changing PLGA and molecular weight and regulate on a large scale.Because PLGA has good biological property and adjustable degraded and drug release behavior, the present invention selects PLGA as pharmaceutical carrier.
minimizing along with polymer volume in bracket coating, the rate of release of medicine will be accelerated, can not steady in a long-termly discharge, the present invention is unexpected to be found the outer surface of resin-coating at support, also avoided in polymer volume causing ground drug release problem faster because polymer volume reduces institute in reducing coating, reached the remarkable result that prevents the violent release of medicine initial stage, and the present invention goes back unexpected the discovery along with polymer volume reduces largely, resin is as long as trace increases, polymer and resinous coat still show and suppress preferably initial stage violent release and slow release effect.Therefore, the lac resin coating add the use amount that has reduced to greatest extent polymer, thereby limited inflammatory reaction, reduced the generation of the untoward reaction such as Restenosis in late period, reduced the risk that advanced thrombus forms.
Above-mentioned resin comprises abietic resin, lac resin, resin acid, ambrosine etc., preferred lac resin.
Lac resin is present known unique a kind of natural animal resin.Oozy purple natural resin after lac insect (Laccifer 1acca) absorption host tree leaves.Claim again Lac, red glue, Lacca etc.Mainly contain lac resin, shellac wax and lac pigment.Lac resin is ester and the polyester mixture that hydroxy fatty acid and hydroxyl sesquiterpenes acid consist of.Can be dissolved in the title barras of ether in lac resin, be insoluble to the title animi resin of ether.Animi resin is mainly by 4 molecule aleutric acids, 1 molecule laccijalaric acid and 3 polyester that the molecule jalaric acid consists of.The monoesters that multiple aliphatic lac acid and terpenes lac acid are arranged in barras.
In the present invention, the main component of lac resin is: aleutric acid (aleuritic acid), olic acid (shellolic acid).
The molecular weight of above-mentioned lac resin is 1000～3000, with the mass ratio of PLGA preferred 1: 200～10: 1, and more preferably 1: 100～5: 1.
The present inventor constantly explores by experiment, and unexpected the discovery avoided drug release relatively too fast or excessively slow when the mass ratio of lac resin and PLGA is in 1: 200～10: 1 scopes, more optimized the release behavior of medicine.Guaranteeing when reducing polymer volume that medicine is long-term slowly discharges, and when experimental results show that quality as lac resin and PLGA was greater than 10: 1, will relatively delay the release time of medicine, and the drug dose at structural transplantation position is reduced relatively; During less than 1: 200, will make drug releasing rate relatively very fast when the mass ratio of lac resin and PLGA, pharmaceutical release time shortens relatively.
Preferred 0.05: 1～2: 1 of said medicine and PLGA mass ratio, more preferably 0.4: 1～2: 1.
Because the mass ratio of medicine and PLGA affects the adhesion between polymer coating and support, the rate of release of medicine, the effective dose of medicine and the time that drug release continues, thereby affect the generation of in-stent restenosis.After the present inventor gropes by continuous experiment, the unexpected discovery when medicine and PLGA are in 0.05: 1～2: 1 scopes of above-mentioned preferred proportioning, both reduced largely polymer volume, increased the mass ratio of medicine and PLGA, also guaranteed the medicine of load abundance on support, made on support that the thickness of polymeric layer is moderate, support has better mechanical performance; On the other hand, make the adhesive attraction between polymer coating and support better, make also that medicine is more long-term slowly to be discharged, the medicine at implant frame position is remained in effective drug level scope for a long time.
When if the mass ratio of medicine and PLGA is too small, be on support the medicine of load abundance, the load capacity of PLGA is increased, relatively increase the generation of inflammatory reaction, the thickness of polymeric layer on support is increased, affect the mechanical performance of support; When if the mass ratio of medicine and PLGA is excessive, polymer coating and relative the reducing of adhesion between support, the slow release effect of medicine also can be affected.
The present invention is the unexpected mass ratio that has improved medicine and PLGA also, makes the amount of coating Chinese medicine reach 2 times of amount of polymers.
Above-mentioned support can also comprise bottom, and described bottom is not for containing the Biodegradable material of medicine, is coated on the bare bracket surface.The preferred polylactic-co-glycolic acid of described Biodegradable material (PLGA).
By increasing bottom, can more strengthen the adhesive force between polymeric layer and bare bracket, thereby avoid better coating stripping or problems of crack on support.
In the present invention, the preferred molecular weight of PLGA is 50,000～120,000, preferably consists of: LA content is that 50%～90%, GA content is that the best proportioning of 10%～50%, LA and GA is (75%～85%): (25%～15%).
When in the present invention, PLGA is in above-mentioned ratio of components and molecular weight ranges, have better biodegradation rate (degradation half life) and drug release behavior, be more convenient for realizing that the medicine long time constant discharges, long term inhibition is propped up the inflammatory reaction of frame peripheral.
The material of above-mentioned bare bracket can be rustless steel, Ni-Ti alloy, cochrome or macromolecular material etc.
Said medicine can be one or more in anti-oxidation medicine, anticoagulants, anticancer class medicine, inhibition vascular smooth muscle cell curing class medicine, anti-inflammatory drug or immune suppressant drug etc.
Wherein, anti-oxidation medicine comprises superoxide dismutase, catalase, coenzyme Q10, glutathion peroxidase etc.;
Anticoagulants comprises aspirin, heparin, clopidogrel and derivant thereof etc.;
Anticancer class medicine comprises colchicine, paclitaxel etc.;
Suppress vascular smooth muscle cell curing class medicine and comprise angiogenic peptide, 17-hydroxy-11-dehydrocorticosterone, calcium ion antagonist etc.;
Anti-inflammatory drug comprises dactinomycin, depsidomycin, KanglemycinC, spergualin, mytiocin, gllooxin etc.;
Immune suppressant drug comprises rapamycin and derivant thereof, Ciclosporin A, ciclosporin C, brefeldin A.
When said medicine was applied to bracket for eluting medicament in the present invention, these two kinds of medicines of clopidogrel or rapamycin all showed better drug releasing rate.
Another object of the present invention is to provide a kind of method for preparing the bracket for eluting medicament with polymeric layer and resin bed, comprise the steps:
1, the PLGA copolymer is dissolved in makes 0.05wt%～5.0wt% solution in organic solvent;
2, add medicine in mentioned solution, after stirring, being uniformly dissolved, filter;
3, above-mentioned filtrate is coated in the bare bracket surface, the PLGA copolymer that this support middle level has and the weight of medicine are that the weight of this support shaft direction per unit length is 10 μ g/mm～200 μ g/mm;
4, resin is dissolved in makes 0.1wt%～1.0wt% solution in organic solvent;
5, with the rack surface of above-mentioned resin-coating in step 3, its weight is that the weight of the axial per unit length of this support is 1 μ g/mm～20 μ g/mm;
6, drying bracket, sterilization.
" wt% " in above-mentioned steps is mass percent.
Organic solvent in above-mentioned steps 1 comprises one or more in acetone, acetonitrile, dichloromethane, chloroform, dimethyl formamide, DMSO etc.
Coating method in above-mentioned steps 3, step 5 can be that ultrasonic spray, immersion or use brush are brushed, and all surfaces, outer surface or the outer surface and the side crack that are coated in bare bracket are surperficial.
The preferred alcohols of organic solvent in above-mentioned steps 4, ketone, phenol, hydro carbons, organic acid equal solvent or the mixed solvent that is got by above solvent preparation.
The present invention also provide a kind of prepare have bottom, the method for the bracket for eluting medicament of polymeric layer and resin bed, comprise the steps:
1, the PLGA copolymer is dissolved in makes 0.05wt%～5.0wt% solution in organic solvent;
2, will state solution stirring, be uniformly dissolved after, filter;
3, above-mentioned filtrate is coated in the bare bracket surface, the PLGA copolymer weight that this support bottom has is that the weight of this support shaft direction per unit length is 0.05 μ g/mm～5.0 μ g/mm;
4, the PLGA copolymer is dissolved in makes 0.05wt%～5.0wt% solution in organic solvent;
5, add medicine in mentioned solution, after stirring, being uniformly dissolved, filter;
6, above-mentioned filtrate is coated in polymer P LGA coating surface, the PLGA copolymer that this support middle level has and the weight of medicine are that the weight of this support shaft direction per unit length is 10 μ g/mm～200 μ g/mm;
7, resin is dissolved in makes 0.1wt%～1.0wt% solution in organic solvent;
8, with the rack surface of above-mentioned resin-coating in step 6, its weight is that the weight of the axial per unit length of this support is 1 μ g/mm～20 μ g/mm;
9, drying bracket, sterilization.
Organic solvent in above-mentioned steps 1 and step 4 comprises one or more in acetone, acetonitrile, dichloromethane, chloroform, dimethyl formamide, DMSO etc.
Above-mentioned steps 3, the coating method in step 6 and step 8 can be that ultrasonic spray, immersion or use brush are brushed, and all surfaces, outer surface or the outer surface and the side crack that are coated in bare bracket are surperficial.
The preferred alcohols of organic solvent in above-mentioned steps 7, ketone, phenol, hydro carbons, organic acid equal solvent or the mixed solvent that is got by above solvent preparation.
The present invention has following advantage and beneficial effect compared to existing technology:
1, the present invention will be widely used in the resin-coating of pharmacy adjuvant in the drug-carrying polymer coating surface, reduced the consumption of polymer, thereby obviously reduced inflammatory reaction, reduced the generation of the untoward reaction such as Restenosis in late period, reduced the formation risk of advanced thrombus.
2, the present invention goes back unexpected the discovery, has farthest improved the mass ratio of medicine and polymer by technical scheme of the present invention, in the situation that reduce polymer volume, has extended on the contrary pharmaceutical release time, has optimized the drug release behavior.
3, the present invention by increasing bottom, has more strengthened the adhesive force between polymeric layer and bare bracket, thereby has avoided better coating stripping or problems of crack on support.
4, the present invention is by the ratio of components of adjusting PLGA and the mass ratio of molecular weight, PLGA and lac resin, make medication coat of the present invention have better biodegradation rate (degradation half life) and drug release behavior, be convenient to realize that the medicine long time constant discharges, long term inhibition is propped up the inflammatory reaction of frame peripheral.
Description of drawings
Fig. 1 contains lac resin and the drug release correlation curve figure that does not contain lac resin
The specific embodiment
The present invention is described in further detail below in conjunction with embodiment and accompanying drawing, but the working of an invention mode is not limited to this.
Embodiment 1
With lactic acid---ethanol copolymer (PLGA, lactic acid/glycolic=50/50, molecular weight 50000) be dissolved in and make 0.05wt% solution in dichloromethane, spray to 316 stainless steel stents surperficial, after having sprayed, it 42 ℃ of lower vacuum drying half an hour, is formed the bottom of bracket coating, and the PLGA weight that the bottom of this bracket coating has is 0.05 μ g/mm in this support shaft direction per unit length weight.
With lactic acid---ethanol copolymer (PLGA, lactic acid/glycolic=50/50, molecular weight 50000) be dissolved in and make 0.5wt% solution in dichloromethane, and drug rapamycin is dissolved in wherein makes 0.2wt% solution, use flush coater to spray, after having sprayed, it 42 ℃ of lower vacuum drying half an hour, is formed the support polymeric layer.Medicine/macromolecule weight ratio=1: 2.5, the PLGA that this support polymeric layer has and the weight of rapamycin are that the weight of this support shaft direction per unit length is 31.11 μ g/mm.
Lac resin (molecular weight 1000) is dissolved in makes 0.1wt% solution in ethanol, same method is coated on the drug-carrying polymer surface with lac resin, and its weight is that the weight of the axial per unit length of this support is 2.22 μ g/mm.
Be placed on 42 ℃ of lower vacuum dryings 48 hours with what prepare.
Embodiment 2
With lactic acid---ethanol copolymer (PLGA, lactic acid/glycolic=75/25, molecular weight 80000) be dissolved in and make 1.0wt% solution in acetone, and drug taxol is dissolved in wherein makes 0.05wt% solution, dip-coating is to the nick-eltitanium alloy stent surface, with it 42 ℃ of lower vacuum drying half an hour, form the polymeric layer of support, medicine/macromolecule weight ratio=0.05: 1, the PLGA that this support polymeric layer has and the weight of medicine are that the weight of the axial per unit length of this support is 186.67 μ g/mm.
Lac resin (molecular weight 2000) is dissolved in makes 0.5wt% solution in ethanol, same method is coated on the drug-carrying polymer surface with lac resin, and its weight is that the weight of the axial per unit length of this support is 6.67 μ g/mm.
Be placed on 42 ℃ of lower vacuum dryings 48 hours with what prepare.
Embodiment 3
With lactic acid---ethanol copolymer (PLGA, lactic acid/glycolic=90/10, molecular weight 120000) be dissolved in and make 5.0wt% solution in THF, with brush, that outer surface and side crack that filtrate brushes the cochrome support is surperficial, with it 42 ℃ of lower vacuum drying half an hour, form the bottom of support, the PLGA weight that this support bottom has is that this support shaft direction per unit length weight is 4.78 μ g/mm.
With lactic acid---ethanol copolymer (PLGA, lactic acid/glycolic=90/10, molecular weight 120000) be dissolved in and make 0.05wt% solution in THF, and drug rapamycin is dissolved in wherein makes 0.1wt% solution, use flush coater to spray, after having sprayed, with it 42 ℃ of lower vacuum drying half an hour, form the polymeric layer of support, medicine/macromolecule weight ratio=2: 1.The PLGA that this support polymeric layer has and the weight of rapamycin are that the weight of the axial per unit length of this support is 13.33 μ g/mm.
Lac resin (molecular weight 3000) is dissolved in makes 1.0wt% solution in ethanol, same method is coated on the drug-carrying polymer surface with lac resin, and its weight is that the weight of the axial per unit length of this support is 19.58 μ g/mm.
Be placed on 42 ℃ of lower vacuum dryings 48 hours with what prepare.
Embodiment 4
With lactic acid---ethanol copolymer (PLGA, lactic acid/glycolic=50/50, molecular weight 50000) be dissolved in and make 4.0wt% solution in dichloromethane, spray to 316 stainless steel stents surperficial, form the bottom of bracket coating, the PLGA weight that the bottom of this bracket coating has is 2.78 μ g/mm in this support shaft direction per unit length weight.
With lactic acid---ethanol copolymer (PLGA, lactic acid/glycolic=50/50, molecular weight 50000) be dissolved in and make 5.0wt% solution in dichloromethane, and the medicine clopidogrel is dissolved in wherein makes 2.0wt% solution, use flush coater to spray, form the support polymeric layer.Medicine/macromolecule weight ratio=2: 5, the PLGA that this support polymeric layer has and the weight of medicine are that the weight of this support shaft direction per unit length is 32.58 μ g/mm.
Lac resin (molecular weight 1000) is dissolved in makes 0.1wt% solution in ethanol, same method is coated on the drug-carrying polymer surface with lac resin, and its weight is that the weight of the axial per unit length of this support is 2.22 μ g/mm.
Be placed on 42 ℃ of lower vacuum dryings 48 hours with what prepare.
With lactic acid---ethanol copolymer (PLGA, lactic acid/glycolic=75/25, molecular weight 80000) be dissolved in and make 3.0wt% solution in acetone, and drug rapamycin is dissolved in wherein makes 1.0wt% solution, dip-coating is to the nick-eltitanium alloy stent surface, form the polymeric layer of support, medicine/macromolecule weight ratio=1: 3, the PLGA that this support polymeric layer has and the weight of rapamycin are that the weight of the axial per unit length of this support is 33.74 μ g/mm.
Lac resin (molecular weight 1000) is dissolved in makes 0.5wt% solution in ethanol, same method is coated on the drug-carrying polymer surface with lac resin, and its weight is that the weight of the axial per unit length of this support is 1.74 μ g/mm.
Be placed on 42 ℃ of lower vacuum dryings 48 hours with what prepare.
Embodiment 6
With lactic acid---ethanol copolymer (PLGA, lactic acid/glycolic=90/10, molecular weight 120000) be dissolved in and make 1.0wt% solution in oxolane, with brush, that outer surface and side crack that filtrate brushes the cochrome support is surperficial, form the bottom of support, the PLGA weight that this support bottom has is that this support shaft direction per unit length weight is 2.78 μ g/mm.
With lactic acid---ethanol copolymer (PLGA, lactic acid/glycolic=90/10, molecular weight 120000) be dissolved in and make 3.0wt% solution in THF, and the medicine dactinomycin is dissolved in wherein makes 1.0wt% solution, use flush coater to spray, form the polymeric layer of support, (medicine/macromolecule weight ratio=1: the 3) PLGA that this support polymeric layer has and the weight of medicine are that the weight of the axial per unit length of this support is 34.28 μ g/mm.
Lac resin (molecular weight 1000) is dissolved in makes 1.0wt% solution in ethanol, same method is coated on the drug-carrying polymer surface with lac resin, and its weight is that the weight of the axial per unit length of this support is 5.58 μ g/mm.
Be placed on 42 ℃ of lower vacuum dryings 48 hours with what prepare.
Comparative Examples 1
Be face coat except not setting up lac resin, carry out the operation identical with embodiment 5.
Comparative Examples 2
With lactic acid---ethanol copolymer (PLGA, lactic acid/glycolic=75/25, molecular weight 80000) be dissolved in and make 2.0wt% solution in acetone, and drug rapamycin is dissolved in wherein makes 1.0wt% solution, dip-coating is to the nick-eltitanium alloy stent surface, form the polymeric layer of support, medicine/macromolecule weight ratio=1: 2, the PLGA that this support polymeric layer has and the weight of rapamycin are that the weight of the axial per unit length of this support is 25.82 μ g/mm.
Lac resin (molecular weight 1000) is dissolved in makes 0.5wt% solution in ethanol, same method is coated on the drug-carrying polymer surface with lac resin, and its weight is that the weight of the axial per unit length of this support is 2.09 μ g/mm.
Be placed on 42 ℃ of lower vacuum dryings 48 hours with what prepare.
Comparative Examples 3
With lactic acid---ethanol copolymer (PLGA, lactic acid/glycolic=75/25, molecular weight 80000) be dissolved in and make 1.5wt% solution in acetone, and drug rapamycin is dissolved in wherein makes 1.0wt% solution, dip-coating is to the nick-eltitanium alloy stent surface, form the polymeric layer of support, medicine/macromolecule weight ratio=1: 1.5, the PLGA that this support polymeric layer has and the weight of rapamycin are that the weight of the axial per unit length of this support is 21.91 μ g/mm.
Lac resin (molecular weight 1000) is dissolved in makes 0.5wt% solution in ethanol, same method is coated on the drug-carrying polymer surface with lac resin, and its weight is that the weight of the axial per unit length of this support is 2.94 μ g/mm.
Be placed on 42 ℃ of lower vacuum dryings 48 hours with what prepare.
Embodiment 7
In-vitro evaluation experiment 1
To be placed in respectively 100ml by the bracket for eluting medicament that experimental example 5 and Comparative Examples 1～3 (seeing Table 1) are made and discharge bottle, add phosphate buffer (pH=7.4) 50ml, close plug, put 37 ℃ of constant temperature DISSOLUTION APPARATUS, start stirring arm, per minute 60 turn, every two days replacing fresh phosphoric salt buffer solutions.At first day, the 3rd day, the 7th day, fortnight was measured its drug release rate by high performance liquid chromatograph in the 28 day respectively.As shown in Figure 1.
Table 1
By Fig. 1, Comparative Examples 1 has identical degradable polymer and medicament contg with embodiment 5, because embodiment 5 has the lac resin coating, therefore shows significant inhibition initial stage violent release effect and slow release effect.
Above-described embodiment is the better embodiment of the present invention; but embodiments of the present invention are not restricted to the described embodiments; other any do not deviate from change, the modification done under spirit of the present invention and principle, substitutes, combination, simplify; all should be the substitute mode of equivalence, within being included in protection scope of the present invention.
Claims (9)
1. bracket for eluting medicament is made of bare bracket, the coating that is coated on support, and it is characterized in that: described coating contains polymeric layer and resin bed at least, and wherein, described polymeric layer comprises polylactic-co-glycolic acid and medicine; Described resin bed is coated on the polymeric layer surface; Described resin is more than one the mixture in balsam, lac resin, resin acid and ambrosine.
2. a kind of bracket for eluting medicament as claimed in claim 1, it is characterized in that: the molecular weight of described lac resin is 1000～3000, with the mass ratio of polylactic-co-glycolic acid be 1: 200～10: 1.
3. a kind of bracket for eluting medicament as claimed in claim 1, it is characterized in that: described medicine and polylactic-co-glycolic acid mass ratio are 0.05: 1～2: 1.
4. a kind of bracket for eluting medicament as claimed in claim 2, it is characterized in that: described medicine and polylactic-co-glycolic acid mass ratio are 0.05: 1～2: 1.
5. a kind of bracket for eluting medicament as described in arbitrary claim in claim 1 to 4, it is characterized in that: the molecular weight of described polylactic-co-glycolic acid is 50,000～120,000; The mass ratio of polylactide and PGA is (50%～90%): (50%～10%).
6. a kind of bracket for eluting medicament as described in arbitrary claim in claim 1 to 4, it is characterized in that: described support also comprises bottom, described bottom is the Biodegradable material that is coated on the bare bracket surface.
7. a kind of bracket for eluting medicament as claimed in claim 5, it is characterized in that: described support also comprises bottom, described bottom is the Biodegradable material that is coated on the bare bracket surface.
8. as the preparation method of the described bracket for eluting medicament of claim 1 to 7 any one, it is characterized in that: comprise the following steps:
(1) polylactic-co-glycolic acid is dissolved in makes 0.05wt%～5.0wt% solution in organic solvent;
(2) add medicine in mentioned solution, after stirring, being uniformly dissolved, filter;
(3) step (2) is filtered gained filtrate and be coated in the bare bracket surface, the polylactic-co-glycolic acid that this support middle level has and the weight of medicine are that the weight of this support shaft direction per unit length is 10 μ g/mm～200 μ g/mm;
(4) resin is dissolved in makes 0.1wt%～1.0wt% solution in organic solvent;
(5) with the rack surface of above-mentioned resin-coating in step (3), its weight is that the weight of the axial per unit length of this support is 1 μ g/mm～20 μ g/mm;
(6) drying bracket, sterilization.
9. the preparation method of a kind of bracket for eluting medicament as claimed in claim 8, it is characterized in that: the organic solvent described in step (1) is the mixture of more than one the above-mentioned solvents in acetone, acetonitrile, dichloromethane, chloroform, dimethyl formamide, DMSO; Coating method described in step (3), step (5) is ultrasonic spray, immersion or uses brush to brush, described " be coated in bare bracket surface " refers to solution is coated in all surfaces, outer surface or outer surface and the side crack surface of bare bracket; Organic solvent described in step (4) is the mixture of more than one the above-mentioned solvents in alcohols, ketone, phenol, hydro carbons, organic acid.
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| CN102166141B (en) * | 2010-07-30 | 2013-08-21 | 深圳市信立泰生物医疗工程有限公司 | Process for preparing drug eluting stent |
| CN102967515B (en) * | 2012-12-14 | 2015-06-03 | 东华大学 | Minimally invasive intravascular stent twisting and bending fatigue simulator and test method thereof |
| CN107496998B (en) * | 2017-08-15 | 2020-12-08 | 北京永益润成科技有限公司 | Peripheral drug eluting stent and preparation and application thereof |
| CN107837428A (en) * | 2017-10-31 | 2018-03-27 | 无锡中科光远生物材料有限公司 | A kind of fungistatic coating material for being sustained antibiotic |
| CN113521023B (en) * | 2021-07-16 | 2023-04-25 | 昆明理工大学 | Preparation method of lac-resin-based intragastric floating retention drug-carrying system |
| CN115645630A (en) * | 2022-11-04 | 2023-01-31 | 湖南埃普特医疗器械有限公司 | Antibacterial catheter and preparation method thereof |
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